We hypothesize that several of the characteristic symptoms and signs of chronic fatigue syndrome (CFS) are associated with neurophysiologic disturbances. These disturbances, which may be causative of symptoms or the result of a poorly understood underlying process, are likely to include disturbances in circadian rhythms and disturbances in autonomic nervous system function. Both the system of circadian rhythms and the autonomic nervous system have been shown to communicate with the immune system through a neuroimmune feedback loop. We will study 20 normal subjects and 20 patients with CFS defined by CDC criteria over a two year period. All subjects will maintain a diary of symptoms relevant to CFS throughout the two year period. Normal subjects will be studied at two randomly chosen time points, and CFS subjects will be studied at baseline and during two periods of exacerbation of illness. We will examine relationships between symptoms of CFS and abnormalities in circadian rhythms (including activity rhythms, core body temperature rhythms, hypothalamic-pituitary-adrenal axis function, and circadian sleep physiology). Both individual circadian rhythms and internal desynchrony of rhythms will be analyzed in relationship to the symptoms of CFS and exacerbations of illness. Characteristic abnormalities in sleep architecture (such as the presence of alpha intrusion into delta sleep and short REM latency) will also be studied in relationship to symptoms and exacerbations of illness. Temporal patterns of internal desynchrony or sporadic variations in the various circadian rhythms will also be examined for trends to determine which circadian oscillator appears to be most closely linked to the expression of symptoms of CFS. We will also assess disturbances in autonomic nervous system function in patients with CFS and correlate abnormalities with symptoms, exacerbations of illness and other neurophysiologic abnormalities. In the third and fourth year of this project, the specificity of neurophysiologic markers found in CFS subjects will be tested by comparing the neurophysiologic profile of CFS subjects with three additional subject groups, a major depression group, an inflammatory disease (active rheumatoid arthritis) group and an allergy group. We hypothesize that patterns of neurophysiologic disturbance seen in CFS will provide a clearer understanding of CFS as a disease entity and a differentiation of CFS from other diseases giving rise to similar symptomatology. Furthermore, elucidation of these disturbances will help us to formulate testable hypotheses regarding the pathophysiologic basis of the disease.